The heterodimeric nuclear cap-binding complex (CBC) binds to the mono-methylated 5′ cap of eukaryotic RNA polymerase II transcripts such as mRNA and U snRNA. binding is important for maturation mRNAs possibly in first round translation nonsense-mediated decay. It also essential export snRNAs metazoans. We report characterization by fluorescence spectroscopy recognition capped human CBC. association constants ( K ) 17 mono- dinucleotide analogs well oligomer m 7 GpppA m2′ pU pA cover range...

Transmembrane domains (TMD) connect the inner with outer world of a living cell. Single TMD containing (bitopic) receptors are particular interest, because their oligomerization seems to be common activation mechanism in cell signaling. We analyzed composition TMDs bitopic proteins within proteomes 12 model organisms. The average number strongly polar and charged residues decreases during evolution, while occurrence dimerization motif, GxxxG, remains unchanged. This may reflect avoidance...

The eukaryotic initiation factor eIF4E binds the mRNA 5′ cap structure and has a central role during translational initiation. mechanisms to control its activity have oncogenic properties thus become targets for anticancer drug development. A recent study (Kentsis et al. 2004) presented evidence that antiviral nucleoside ribavirin phosphorylated derivatives were structural mimics of cap, high-affinity ligands eIF4E, potent repressors eIF4E-mediated cell transformation tumor growth. Based on...

Colloidal quantum dots (QDs) are nanoparticles that able to photoreduce redox proteins by electron transfer (ET). QDs also energy resonance (RET). Here, we address the question of competition between these two routes QDs' excitation quenching, using cadmium telluride and cytochrome c (CytC) or its metal-substituted derivatives. We used both oxidized reduced versions native CytC, as well fluorescent, nonreducible Zn(II)CytC, Sn(II)CytC, metal-free porphyrin CytC. found all CytC quench QD...

Background: Epilepsy affects millions of people worldwide, yet we still lack a successful treatment for all epileptic patients. Most the available drugs modulate neuronal activity. Astrocytes, most abundant cells in brain, may constitute alternative drug targets. A robust expansion astrocytic cell bodies and processes occurs after seizures. Highly expressed astrocytes, CD44 adhesion protein is upregulated during injury suggested to be one important proteins associated with epilepsy. It...

The release of influenza RNA inside the host cell occurs through fusion two membranes, viral envelope and that cellular endosome. is mediated by hemagglutinin protein (HA), in particular peptide (HAfp) located N-terminal fragment HA2 subunit. This anchors internal endosomal membrane, whereas C-terminal part comprises a transmembrane domain (TMD) embedded envelope. A drop pH endosome acts as main trigger for large conformational change leads to anchoring peptide, close contact membranes...

While quantum dots (QDs) are useful as fluorescent labels, their application in biosciences is limited due to the stability and hydrophobicity of surface. In this study, we tested two types proteins for use a cover spherical QDs, composed cadmium selenide. Pumilio homology domain (Puf), which mostly α-helical, leucine-rich repeat (LRR) domain, rich β-sheets, were selected determine if there preference one these secondary structure nanoparticle covers. The protein sequences optimized improve...

To quantitatively examine the effect of membrane organization on lateral diffusion, we studied fluorescent carbocyanine lipid analogues and EGFP-tagged, single-pass transmembrane proteins in systems decreasing complexity: (i) plasma (PM) living cells, (ii) paraformaldehyde/dithiothreitol-induced giant vesicles (GPMVs), (iii) unilamellar (GUVs) under physiological buffer conditions. A truncated, signaling-deficient interleukin-4 receptor subunit, showing efficient accumulation membrane,...

Ferredoxin:NADP+ oxidoreductase (FNR) is a plant and cyanobacterial photosynthetic enzyme, also found in non-photosynthetic tissues, where it involved redox reactions of biosynthetic pathways. In vivo transfers electrons to nicotinamide adenine dinucleotide phosphate (NADP+), forming its reduced version, NADPH, while vitro can use NADPH reduce several substrates, such as ferricyanide, various quinones nitriles. As an catalyzing reaction broad range FNR may be used biotechnological processes....

The development of targeted anticancer drugs has been one the most challenging goals current research. Eukaryotic translation initiation factor 4E (eIF4E) is an oncogene that stimulates mRNA via binding to 5′ endcap structure. It well documented eIF4E overexpressed in many cancers including breast, prostate, head and neck, stomach malignancies leads oncogenic transformation metastasis. One approach block function cancer cells based on disruption interaction between cap structure using analog...

Colloidal CdTe quantum dots may photoreduce both heme and iron–sulfur cluster containing proteins. Reduction level be tuned by choosing different size of nanocrystals.

Aryloxy triester phosphoramidate methodology, commonly known as ProTide technology, is one of the most widely used prodrug approaches applied to therapeutic nucleosides. This approach has been extensively by pharmaceutical industry and researchers in medicinal chemistry. Herein we report our adaptation this effective method for synthesis bioactive 5'-mRNA cap analogues inhibitors targeting cap-dependent translation. The was performed two main stages: preparation N2-modified guanosine their...

Cleavage of hemagglutinin precursor (HA0) by cellular proteases results in the formation two subunits, HA1 and HA2. The N-terminal fragment HA2, named a fusion peptide (HAfp), possess charged, amine N-terminus. It has been shown that N-terminus HAfp stabilizes structure helical hairpin observed for 23-amino acid long (HAfp1-23), whose larger activity than HAfp1-20 demonstrated recently. In this paper, we analyze effect charge on peptide-mediated efficiency conformation changes at membrane...

An assignment of the helical hairpin influenza fusion peptide has been made based on hydrophobic moments, represented in a form two‐dimensional map. Such holds for all serotypes, even cases mutations altering amino acid character. Similar results are obtained experimentally developed hydrophobicity scales, whose values reflect transfer energies between aqueous and membrane environments. A distinct, however still structure‐related map corresponds to contiguous HIV gp41 fp. The method may be...

Hemagglutinin (HA) is a class I viral membrane fusion protein, which the most abundant transmembrane protein on surface of influenza A virus (IAV) particles. HA plays crucial role in recognition host cell, envelope and cell membrane, major antigen immune response during infection. Mature organizes homotrimers consisting sequentially highly variable globular head relatively conserved stalk region. Every monomer comprises hydrophilic ectodomain, pre-transmembrane domain (pre-TMD), hydrophobic...

In the search for new options pharmacological treatment of major depressive disorder, compounds with a rapid onset action and high efficacy but lacking psychotomimetic effect are particular interest. present study, we evaluated antidepressant potential NitroSynapsin (NS) at behavioural, structural, functional levels. NS is memantine derivative dual allosteric N-methyl-d-aspartate receptors (NMDAR) antagonist using targeted delivery by aminoadamantane warhead nitro group to inhibitory redox...

Fusion of viral and host cell membranes is a critical step in the life cycle enveloped viruses. In case influenza virus, it mediated by subunit 2 hemagglutinin (HA) glycoprotein whose N-terminal fragments insert into target membrane initiate lipid exchange. These isolated fragments, known as fusion peptides (HAfp), already possess own fusogenic activity towards liposomes. Although they have long been studied with hope to uncover details HA-mediated fusion, their actual mechanism action...